To the Editor: We refer to the paper by Okwi et al. (1) Cost
benefit analysis of screening for sickle cell disease (SCD) using
different methods cannot be done in isolation, and the following are
important principles to take into account.

1. Reasons for screening: (i) early detection of the disease for
timely intervention to minimise morbidity and mortality; (ii) patient
and family education on SCD; (iii) genetic counselling as part of a
long-term strategy to prevent live homozygous SCD (SS) births; and (iv)
short- and long-term cost saving by means of (i), (ii) and (iii) above.

2. The method of detection needs to be very sensitive. Subjects
with false-negative results will remain undiagnosed and may well present
with an acute crisis or organ damage, with major cost implications.

The sensitivities of the sickling and solubility tests for
detection of the sickle cell trait (AS) as reported by the authors were
65% and 45%, respectively, essentially translating to high 35% and 65%
false-negative rates, an unacceptable scenario regardless of cost
saving.

Clearly the methodologies need to be questioned, since the sickling
test is sensitive enough to detect AS.1,2 In addition, the article
advocates that negative sickling tests be regarded as negative for the
disease, evidently with no further testing required. This means that 35%
of the subjects tested will walk around with undiagnosed AS despite
having been tested, which defeats the objectives of screening as stated
above.

The recommendation by the group that the sickling test be the
preferred and sole method for screening, purely on the basis of
economics, is disconcerting, while with its observed shortcomings the
proposed screening method would be of short-term benefit.

We conclude that a cost benefit analysis of methods with such low
sensitivities is ineffective and futile.

N A Alli

S B Loonat

Department of Molecular Medicine and Hematology School of Pathology

University of the Witwatersrand/National Health Laboratory Service
Johannesburg

Okwi et al. reply: Our cost benefit analysis was not done in
isolation, as suggested above. The paper was published together with
others that appeared elsewhere and addressed the issues raised.
Sensitisation of communities (patient and family education on SCD) and
timely intervention were covered in a publication in the East African
Medical Journal. (1) Another paper addressing some of these issues was
published in BMC Blood Disorders. (2)

All the false negatives with the sickling test were cases of AS
(carriers), not SS. The sickling test demonstrated all SS cases, as did
Hb electrophoresis--i.e. sickling was sensitive in SS detection but not
in AS detection. The sickling test would therefore be sensitive enough
to detect all the children with SS, who would benefit most since they
suffer from crisis, while carriers (AS) do not.

Lastly, the authors state that our article advocated interpreting a
negative sickling test as the patient being negative for the disease,
with no further testing required. We did not assume or recommend this.
Our assumption was that all the children who might accidentally be
missed by the sickling test and develop symptoms later would be tested
by Hb electrophoresis.

We concluded that although the sickling test was not highly
sensitive, it was more sensitive than solubility and the peripheral
blood film method.